Porphyria

Dr. med. Mira Seidel is a freelance writer for the medical team.

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Porphyria is a group of rare metabolic diseases that are associated with impaired formation of the red blood pigment heme. Typical symptoms of porphyria are colicky abdominal pain and severe skin sensitivity to light. Most porphyrias are hereditary and can therefore only be treated symptomatically. You can find out more about porphyria here.

ICD codes for this disease: ICD codes are internationally recognized codes for medical diagnoses. They can be found, for example, in doctor's letters or on certificates of incapacity for work. E80

Porphyria: description

Porphyries are rare and little known. They form a group of related metabolic diseases and manifest themselves primarily on the skin and the nervous system.

Metabolism is the sum of all biochemical processes in the body in which substances are built up, broken down and converted. Enzymes are involved in these processes, each processing a step in the reaction chain. Many different metabolic pathways take place in the human body - one of them is the build-up of heme, which the body needs for red blood cells, among other things. The heme consists of a so-called porphyrin - an organic chemical compound of which there are several in nature - with an iron ion in the middle.

In the metabolic disease porphyria, the heme cannot be formed normally due to an enzyme defect. The result is that the heme precursors build up because they cannot be further processed. These precursors are also porphyrins - hence the name of the disease.

Why is the porphyrin heme important?

Heme is an important component of hemoglobin - the red blood pigment in red blood cells that is responsible for transporting oxygen in the blood: Hemoglobin is made up of a protein complex with a central heme group. The iron ion from the heme can bind molecular oxygen.

Heme is also part of the red muscle pigment myoglobin and the cytochrome. These are enzymes that are of crucial importance in the breakdown of drugs.

Porphyria forms

There are seven different types of porphyria - four acute and three non-acute variants.

The four acute forms of porphyria are:

acute intermittent porphyria,
the Porphyria variegata,
hereditary coproporphyria and
the very rare Doss porphyria.

They are called acute because they suddenly experience abdominal pain that can last for several days. With porphyria variegata and hereditary coproporphyria, those affected also suffer from skin sensitivity to light.

The three non-acute types of porphyria, on the other hand, show no acute abdominal pain and mainly affect the skin. These include:

the Porphyria cutanea tarda,
erythropoietic protoporphyria and
the rare congenital erythropoietic porphyria (Günther's disease).

The formation of heme takes place mainly in the bone marrow and to a lesser extent in the liver. Therefore, the seven forms of porphyria can be divided into two groups, depending on the place where the heme precursors mainly accumulate due to an enzyme defect. Accordingly, one differentiates:

erythropoietic porphyrias (bone marrow): erythropoietic protoporphyria, congenital erythropoietic porphyria (Günther's disease)
Hepatic porphyrias (liver): acute intermittent porphyria, porphyria variegata, hereditary coproporphyria, Doss porphyria, porphyria cutanea tarda

Porphyria: frequency

Only two forms, porphyria cutanea tarda and acute intermittent porphyria, occur in adulthood with any significant frequency. Erythropoietic protoporphyria is the most common form of porphyria that occurs in childhood. All other forms are very rare.

Porphyria: symptoms

Depending on where the enzyme defect is, different symptoms of porphyria manifest themselves. The signs of the three most common forms of porphyria are:

Acute Intermittent Porphyria (AIP)

Acute intermittent porphyria is characterized by a variety of symptoms, which is why it is often difficult for the doctor to make the correct diagnosis. The severity of this form of porphyria varies greatly: While 90 percent of the cases are asymptomatic (i.e. without symptoms), there are always cases of illness with paralysis, which can lead to death if the respiratory muscles are affected.

The disease mainly causes acute abdominal pain as well as neurological and psychiatric symptoms. As the term intermittent suggests, these often occur in bursts. Drugs, hormonal changes (such as pregnancy, menstruation) or a lack of carbohydrates through diet or fasting usually trigger such acute attacks. An acute attack usually only lasts one to two weeks, but can last significantly longer if symptoms of paralysis occur.

This is what an acute episode looks like:

Violent colicky abdominal pain, which is mostly localized in the lower abdomen and signals the beginning of a flare-up.
fever
Vomiting and chronic constipation that is difficult to treat.
Reddish urine that turns darker after a while (dark spots in your underwear!)
Neurological symptoms such as incomplete (paresis) or complete paralysis (paralysis), muscle weakness and sensory disorders (i.e. disorders in the area of vision, hearing, taste, smell and sense of balance)
Mental mood swings, delusions, coma and states of confusion (delirium)
Cardiovascular problems such as racing heart (tachycardia) and high blood pressure (hypertension)

Porphyria cutanea tarda

In porphyria cutanea tarda, the heme precursors (porphyrins) accumulate in the liver, pass into the blood and thus reach the skin. The result is a strong sensitivity to light: The UV rays in sunlight cause skin vesicles to form on unprotected skin areas such as hands, face and neck. Since the skin is also very vulnerable, such fluid-filled blisters can form even with the smallest injuries and everyday work. The vesicles burst and heal to form bright, raised scars. Otherwise, the skin is brownish in color due to embedded porphyrins.

People may also have excess hair on the forehead, cheeks, and around the eyes (hypertrichosis).

The patients also often suffer from liver disease (such as fatty liver or liver cirrhosis). The urine of the patient may be brown-red in color.

Erythropoietic Protoporphyria (EPP)

The skin is extremely sensitive to light: the porphyrin, which cannot be further built up into heme due to the enzyme defect, circulates in the blood. When exposed to sunlight, it forms oxygen radicals in the skin, which lead to burn-like symptoms on the skin with itching and pain. Just a few minutes of sunlight can trigger the skin symptoms. Indirect light, such as from reflective surfaces, can also cause discomfort. The damaged skin can regenerate completely, but this can take hours to days. Glycoproteins can accumulate in the mostly unprotected areas of the skin such as the nose or hands, causing the skin to thicken and coarsen.

In addition, some of those affected suffer from impaired liver function, which in ten percent of cases develops into a chronic disease of the liver, liver cirrhosis.

Porphyria: causes and risk factors

The formation of heme takes place via eight different reaction steps. Each step is made possible by a specific enzyme; seven of the eight enzymes can be defective - porphyria is present.

The intermediate products (heme precursors) that are formed in the reaction chain before the defective enzyme cannot be processed further and accumulate. Most of the time, however, the heme production path is only partially blocked and is balanced by regulatory mechanisms so that the heme formation works at least partially. Nevertheless, heme precursors (porphyrins) accumulate, which can cause various symptoms - mostly in the form of porphyria attacks, triggered by certain factors such as infections or the use of medication.

Why porphyrins make you sick

The heme precursors, which cannot be processed further, are deposited in the organs, especially in the skin and liver. In addition, the porphyrins are usually excreted in large quantities with the stool and urine. A red or orange colored urine is therefore a typical symptom of some forms of porphyria.

The accumulation of heme precursors in acute porphyrias mainly leads to complaints in the area of the abdomen and nervous system. In the case of non-acute porphyrias, however, skin changes are in the foreground.

Genetic change as the cause of porphyria

With porphyria the genetic material (gene) of the defective enzyme is changed by a mutation. This mutation is inherited in most cases and is generally autosomal dominant, i.e. independent of the sex chromosomes. Usually, however, the porphyria only manifests itself together with external influences such as alcohol consumption, certain medications or infections.

In some cases, porphyria is acquired through poisoning (such as lead poisoning).

Acute Intermittent Porphyria (AIP)

Acute intermittent porphyria is the most common acute porphyria. Women are three times more likely to be affected than men. As a rule, this form of porphyria is only noticed between the ages of 20 and 40.

In acute intermittent porphyria, the third enzyme in the heme production path, porphobilinogen deaminase, is defective. This defect is inherited as an autosomal dominant trait. Symptoms usually only arise when factors such as certain medications, alcohol or infections are added. These then trigger an acute flare-up of illness (“intermittent” means occurring at times).

Porphyria cutanea tarda

Porphyria cutanea tarda is the most common form of porphyria and is also inherited as an autosomal dominant trait. It can be inherited heterozygous (genetic defect on one of the two paired chromosomes) or homozygous (genetic defect on both chromosomes). Men are affected twice as often as women. The disease usually becomes noticeable from the age of 40.

In this form of porphyria, the fifth enzyme, uroporphyrinogen decarboxylase, is affected by the disorder. People with this defect often do not even notice the disease. Symptoms are only triggered when the liver is stressed. Alcohol is responsible for the overuse of the liver in two thirds of the cases. But there are also other triggers such as medication, for example estrogens in the contraceptive pill.

Erythropoietic Protoporphyria (EPP)

In the rare erythropoietic protoporphyria, the enzyme defect is in the last step of the heme formation, the incorporation of the iron ion. The main consequence is that the skin is very sensitive to light. Erythropoietic protoporphyria often occurs for the first time in childhood.

Porphyria: examinations and diagnosis

Due to the complexity of the disease and the varied symptoms, it can be for one too experienced doctor difficult be able to make the correct diagnosis. The typical porphyria symptoms and information about similar clinical pictures in relatives are particularly important. For a precise diagnosis of porphyria, blood, urine and stool are examined for porphyrins. The examination should ideally be carried out when the person concerned is currently experiencing symptoms, as the values change in the course of the disease and can even drop to a normal value. Further important diagnostic steps in the clarification of porphyria:

Acute intermittent porphyria (AIP)

In acute intermittent porphyria, the urine turns red to dark red when left standing for a long time. However, this proof is only successful in two thirds of the cases. Another screening test is the Ehrlich reverse aldehyde test. One drop of urine is added to one milliliter of Ehrlich's reagent. If there is an acute intermittent porphyria, the color is cherry-red.

Porphyria cutanea tarda

It is characterized by an enlarged liver, which is usually palpable. The ultrasound examination usually reveals fatty liver or liver cirrhosis. A liver biopsy can also be informative. A small tissue sample is taken from the liver with a hollow needle under local anesthesia. In Porphyria cutanea tarda, the tissue sample fluoresces red under a UV lamp. If it is then examined with a microscope, an increased accumulation of iron (iron storage disease = siderosis), fatty liver, chronic liver inflammation or liver cirrhosis can sometimes be seen.

Erythropoietic Protoporphyria (EPP)

The symptoms described often suggest that there is an erythropoietic protoporphyria. This suspicion can be confirmed by a blood analysis. This involves examining heparin blood, which is uncoagulated blood from red blood cells and blood plasma, for free protoporphyrin, a precursor of heme. Sometimes stool samples are also tested for protoporphyrin.

Porphyria: treatment

It is important to distinguish the various porphyries as they are treated differently. The following applies to all of them: The respective enzyme defect is genetic and therefore cannot be cured. Therapy is therefore symptomatic, i.e. only the symptoms can be alleviated. The aim is also to avoid triggering factors (exposure prophylaxis).

Acute intermittent porphyria (AIP)

With a confirmed diagnosis and severe attacks, those affected may need to be monitored by intensive care medicine, as there is a risk of respiratory paralysis. Acute relapse triggers, such as certain medications, must be discontinued. In addition, glucose or heme arginine is given via an infusion, which leads to the excretion of accumulated heme precursors. To calm down and relieve pain, patients are treated with salicylates and morphine derivatives, for example. So-called β-receptor blockers (beta blockers) and reserpine help against palpitations and high blood pressure.

Porphyria cutanea tarda

In the case of porphyria cutanea tarda, a consistent avoidance of the triggering factors such as alcohol and estrogen (as in the pill) can improve the symptoms. In addition, those affected should protect themselves from the sun with sun protection ointments and clothing.

Bloodletting, in which 500 milliliters of blood are drained once a week, can also be helpful. The aim is to flush the accumulated porphyrin out of the liver. With a total of four to eight liters of bloodletting, the patient's condition normalizes in most cases. Those affected should drink at least one and a half liters a day to compensate for the loss of fluid. If there is cirrhosis of the liver, bloodletting must not be performed, as too many proteins would be lost.

If the course is severe, chloroquine therapy is recommended. Chloroquine, originally a drug used to treat malaria, binds porphyrin, which is excreted by the kidneys. This is how porphyrin can be easily removed from the body. If the liver is functioning well, chloroquine administration of 500 milligrams per day is recommended for one week.

Erythropoietic Protoporphyria (EPP)

Important measures are sun protection through clothing and special sun protection creams as well as avoiding triggering factors (such as alcohol, medication).

A phototherapy at the dermatologist's in spring can make the skin more tolerant to sunlight: The skin is carefully irradiated with artificial UV light several times a week. This makes her a little thicker and gives her a light complexion.

Some people can relieve the symptoms of erythropoietic protoporphyria by taking beta-carotene, an orange natural pigment. It can neutralize the reactive oxygen in the skin caused by light and improve the symptoms. However, when ingested, the skin usually turns a little orange.

The drug afamelanotide is a new therapy and stimulates skin tanning. The skin pigment melanin is increasingly formed, which is stored in the skin. A high level of melanin in the skin can increase the amount of time the person can be exposed to the sun. Afamelanotide is showing good results and can greatly improve the quality of life. However, this drug has not yet been approved in Germany.

Liver transplantation must be considered if cirrhosis of the liver develops.

Porphyria: prevention

Porphyria cannot be prevented because the disease is genetic. However, those affected can do something themselves to prevent symptoms of porphyria.

Acute intermittent porphyria (AIP)

Most acute flare-ups can be avoided by taking consistent precautionary measures.

Medication: Certain medications can trigger an acute flare-up. Therefore, speak to your doctor before taking any medication and also when using home remedies or plant substances. It is best to avoid medication entirely. If this is not possible in the case of a serious illness, for example, the doctor will prescribe suitable medication after weighing the benefits and risks and in consultation with a porphyria specialist.

Alcohol: Patients are strongly advised not to consume alcohol. For some, it can be very difficult to avoid alcohol in the long term. However, you need to keep in mind that any flare-up can be potentially life-threatening.

Diet: Dieting or fasting can lead to an acute flare-up. It is therefore very important to maintain a regular diet and maintain your weight. People with severe porphyria who have had multiple relapses should seek help from their doctor and a nutritionist.

Porphyria cutanea tarda and erythropoietic protoporphyria (EPP)

With both forms of porphyria, it is important to avoid the sun as much as possible:

Clothing: A simple sun protection measure is to wear long-sleeved, tightly woven clothing, a hat, closed shoes, and gloves.

Sun cream: Normal sun creams are not suitable because they absorb the light in the UV range, but not the blue part of the visible light, which also damages the skin. You should therefore only use special sun protection creams based on titanium dioxide and zinc oxide, as these protect against UVA, UVB and visible light.

These simple measures can reduce the risk of a porphyria flare-up. Most people only have one or two flare-ups in their lives. The risk of having a flare-up decreases with age - but porphyria never goes away completely.

Porphyria: disease course and prognosis

The severity of porphyria varies. For most of those affected, a largely normal life is possible if they observe certain things. Others suffer from severe, painful sensitivity to light and liver dysfunction.

Acute intermittent porphyria (AIP)

Most people who have one or more flare-ups make a full recovery and only need to take a few precautions. Repetitive attacks occur frequently in less than ten percent of cases. If symptoms of paralysis occur, it can take several weeks to many months for them to resolve.

Erythropoietic Protoporphyria (EPP)

Patients with EPP should see their doctor regularly (at least once a year) to have their liver tested for possible damage from accumulated porphyrin using a blood test. While this is rare, it should be recognized as early as possible, as erythropoietic protoporphyria is fatal in ten percent of cases.

Porphyria cutanea tarda

The course of this form of porphyria is usually favorable, but it depends on how severely the liver is damaged and whether certain drugs (as a trigger) are consistently avoided.

Patients with this type of porphyria have an increased risk of liver cell cancer.

Tags: nourishment alcohol organ systems